Diabetes is a major cause of end stage renal disease. Early in the course of clinical and experimental diabetes the kidneys enlarge and function at supernormal levels. These early events may be manifestations of the same process which ultimately leads to the development of diabetic nephropathy. Relatively little is known about the basic biological events which initiate these anatomical and physiological alterations. The general objective of this proposal is to examine the potential importance of eicosanoids in renal growth, function and the development of nephropathy in experimental diabetes. The amount and nature of dietary fat had been found to have profound effects on renal eicosanoid synthesis in nondiabetic animals and man, but similar studies in experimental diabetes are lacking. Preliminary data are presented which indicate that a diet rich in eicosapentaenoic acid, a polyunsaturated fat found in fish oil, interferes with arachidonic acid metabolism and markedly enhances renal growth in experimental diabetes. Experiments are proposed to examine the effects of two dietary fats, eicosapentaenoic acid and linoleic acid, on renal fatty acid metabolism. Expansion of preliminary observations of the effects of eicosapentaenoic acid on renal growth and function are proposed. Finally, long-term studies are planned to evaluate the effects of these two dietary fats on the rate of development of diabetic nephropathy by assessment of proteinuria, renal function and glomerular basement membrane thickness. The results of these studies will add new information regarding the impact of dietary fat on renal fatty acid metabolism and dienoic eicosanoid synthesis in experimental in the basic biological events regulating renal growth and function. Furthermore, the results of experiments examining the impact of dietary fat on the rate of development of diabetic nephropathy may serve as the basis for clinical studies to evaluate the importance of this factor in human diabetic kidney disease.